Preemptive adefovir versus lamivudine for prevention of hepatitis B reactivation in chronic hepatitis B patients undergoing chemotherapy

Background This proof-of-concept study compared lamivudine (LAM) with a newer antiviral agent, adefovir dipivoxil (ADF), in preventing hepatitis B virus (HBV) reactivation in chronic HBV patients undergoing chemotherapy. Methods Hepatitis B surface antigen (HBsAg) positive patients intended to undergo chemotherapy were randomized to receive either LAM 100 mg daily or ADF 10 mg daily. Anti-viral therapy was started 1 week prior to chemotherapy and until 6 months after completing chemotherapy. The primary outcome was HBV reactivation rate. All patients with viral breakthrough were screened for resistance mutations by direct sequencing. Results Seventy treatment-naïve patients were consecutively randomized 1:1 to LAM or ADF. The median baseline HBV DNA levels were similar (LAM 3.36 vs. ADF 3.17 log 10 copies/mL, p = 0.860). The median duration was 8.3 months on LAM and 10.6 months on ADF ( p = 0.220). HBV reactivation was observed in 13/35 (37.1 %) on LAM compared with 10/35 (28.6 %) on ADF ( p = 0.611). The median time to HBV reactivation was 4.6 and 8.1 months, on LAM and ADF respectively. Among these 13 patients, 8/13 (61.5 %) on LAM had developed drug resistance mutations but none on ADF had developed drug resistance mutations to ADF ( p = 0.003). Both drugs were well tolerated and no severe drug-related toxicities were reported. Conclusion In this randomized clinical study, adefovir and lamivudine demonstrated similar efficacy in preventing hepatitis B reactivation in HBsAg-positive patients undergoing chemotherapy. In patients whose hepatitis B reactivated, adefovir was associated with a lower resistance profile.